Effects of Anatolian Propolis and Hypertonic Saline Combination Nasal Spray on Allergic Rhinitis Symptoms: A Prospective, Multicenter Study.

Objectives: This study aimed to evaluate how Rhinapi nasal spray affects symptoms of allergic rhinitis. Methods: In this prospective, multicenter, observational study, 10,000 patients (comprising 5028 males and 4972 females) exhibiting symptoms of allergic rhinitis (namely, nasal discharge, sneezing, nasal itching, and nasal obstruction) from different centers in different regions of Turkey were enrolled in the study between March 2022 and March 2023. All the patients wanted to participate in the study and were administered Rhinapi one puff to each nostril three times a day, for a period of 3 weeks. Total symptom scores, quality of life (QoL) scores, and otolaryngological examination scores were evaluated before and 3 weeks after treatment. Results: The scores for discharge from the nose, sneezing, nasal pruritus, and blockage of the nose all indicated improvement when compared to pre-medication and post-medication. This difference achieved statistical significance (P < .001). The mean total symptom score fell following treatment (P < .001): whilst the score was 11.09 ± 3.41 before administering Rhinapi; after administration, the average score was 6.23 ± 2.41. The mean QoL scores also altered after medication (P < .001), improving from a mean value of 6.44 ± 1.55 to a mean of 7.31 ± 1.24. Significant improvement was also noted in the scores for conchal color and degree of edema after the treatment had been administered (P < .001). Conclusion: The study demonstrates that Rhinapi nasal spray decreases total symptom scores, and results in improved QoL and otolaryngological examination scores. Propolis spray may be recommended for patients with allergic rhinitis alongside other treatments.

Post Surgical Outcomes in Paediatric Adenotonsillar Hypertrophy with Obstructive Sleep Apnea: Subjective and Objective Evaluation.

The aim of the study was to determine the post surgical outcomes in pediatric adenotonsillar hypertrophy with OSA using portable polysomnography (PSG), OSA 18 Questionnaire and Quality of life (QoL) scores. Secondly to correlate the subjective outcomes with objective scores of polysomonography. A prospective, single-arm, nonrandomized, single center study was performed at a tertiary care centre on children aged 3-12 years (n = 30) with adenoid hypertrophy/ tonsillar hypertrophy/adenotonsillar hypertrophy and symptoms suggestive of OSA. All subjects underwent appropriate surgical intervention. A portable PSG and OSA 18 questionnaire evaluation was performed pre surgery and 06 weeks post surgery to assess objective and clinical assessment for OSA. The mean age of children enrolled in the study was 8.68 ± 3 years. The mean pre treatment AHI was 12.56 ± 13.16 which improved to 1.72 ± 1.53 post surgery and was statistically significant (p < 0.05, Wilcoxon signed rank test). There was a statistically significant improvement in other PSG indices such as RDI and ODI post surgery also. The mean total symptom score (TSS) and QoL score also showed a statistically significant improvement post treatment (p < 0.05). However there was no correlation between the PSG and OSA 18 questionnaire scores pre and post surgery. Children with OSA like symptoms can undergo a portable polysomnography pre and post surgery to demonstrate severity of OSA and objectively monitor improvement in OSA post treatment. In the absence of availability of PSG, OSA 18 questionnaire is a suitable alternative to monitor disease severity and outcomes. Further studies may plan to include impact of paediatric OSA on other function such as the cardiac, dentition & malocclusion and neurocognitive function.

Efficacy and safety of fixed-dose combination of Bilastine-Montelukast in adult patients with allergic rhinitis: a phase III, randomized, multi-center, double-blind, active controlled clinical study.

BACKGROUND: Histamine and cysteinyl leukotrienes (CysLTs) are potent inflammatory mediators in allergic rhinitis (AR). Studies involving other combinations of antihistaminics (Levocetirizine) and highly selective leukotriene receptor antagonist (LTA) (Montelukast) combination have shown additive benefits and are widely prescribed for AR. OBJECTIVE: Evaluate the efficacy and safety of Bilastine 20 mg and Montelukast 10 mg fixed-dose combination (FDC) therapy in patients with AR. METHODS: A randomized, double-blind, comparative, parallel, phase III study was conducted to evaluate efficacy and safety of Bilastine 20 mg and Montelukast 10 mg FDC at 16 tertiary care otolaryngology centres in India. Adult patients with AR for one year with IgE antibody positive and 12-h NSS score >36 in 3 days were randomized to receive either Bilastine 20 mg and Montelukast 10 mg or Montelukast 10 mg & Levocetirizine 5 mg tablets for 4 weeks. The change in total symptom score (nasal symptom scores (NSS) & non-nasal symptom scores (NNSS)) from baseline to week 4 was assessed as primary endpoint. Secondary endpoints included changes in TSS, NSS, NNSS, individual symptom scores (ISS), Rhinoconjunctivitis Quality of Life (RQLQ), discomfort due to rhinitis (VAS), and clinical global impression (CGI) scores. RESULTS: The change in mean TSS from baseline to week 4 in Test group (16.6 units) was comparable to reference group (17 units) (p= 0.8876). The difference in change in mean NSS, NNSS and ISS from baseline to day 7, 14, 28 were comparable. RQLQ improved from baseline to Day 28. Significant improvements were observed in discomfort due to AR measured by VAS and CGI scores from baseline to day 14 and 28. The safety and tolerability of patients were comparable between the groups. All adverse events (AEs) were mild to moderate in severity. No patient discontinued due to AEs. CONCLUSIONS: The FDC of Bilastine 20 mg and Montelukast 10 mg was efficacious and well tolerated in Indian patients with AR.

Effects of Dapagliflozin in Asian Patients With Heart Failure and Reduced Ejection Fraction in DAPA-HF.

Background: Patients with heart failure with reduced ejection fraction (HFrEF) in Asia exhibit many differences from those in other parts of the world. Objectives: This study sought to investigate the efficacy and safety of dapagliflozin, compared with placebo, in HFrEF patients in Asia, compared with those elsewhere, enrolled in the DAPA-HF (Dapagliflozin and Prevention of Adverse-outcomes in Heart Failure) trial. Methods: Patients in New York Heart Association functional class II to IV with a left ventricular ejection fraction ≤40% and elevated N-terminal pro-B-type natriuretic peptide were eligible for the DAPA-HF trial. The primary outcome in the DAPA-HF trial was the composite of an episode of worsening HF (HF hospitalization or urgent HF visit requiring intravenous therapy) or cardiovascular death. Results: Of the 4,744 patients in the DAPA-HF trial, 1,096 (23.1%) were enrolled in Asia; 721 (15.2% overall, 65.8% of patients in Asia) were enrolled in East Asia (237 in China, 343 in Japan, and 141 in Taiwan), 138 (2.9% overall, 12.6% in Asia) in South-East Asia (Vietnam), and 237 (5.0% overall, 21.6% in Asia) in South Asia (India). Patients from Asia had similar rates of worsening HF events and mortality compared with patients elsewhere. Compared with placebo, dapagliflozin reduced the risk of the primary endpoint to the same extent in patients from Asia (HR: 0.65; 95% CI: 0.49 to 0.87) as elsewhere (HR: 0.77; 95% CI: 0.66 to 0.89) (P for interaction = 0.32). Consistent benefits were observed for the other prespecified outcomes and among the regions of Asia. Study drug discontinuation and prespecified adverse events did not differ between regions. Conclusions: Dapagliflozin, compared with placebo, reduced the risk of worsening HF events and cardiovascular death to the same extent in Asian patients as elsewhere. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]; NCT03036124).

The Impact of Bilastine on Symptoms of Allergic Rhinitis and Chronic Urticaria: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Allergic diseases are immunological exaggerations with symptoms that may interfere with life quality. Bilastine, a novel oral second-generation H-1 antihistamine, is highly selective to H-1 receptors and has anti inflammatory properties. The present evidence regarding the drug efficacy is inconsistent. OBJECTIVES: We aimed to evaluate the efficacy and safety of bilastine compared with the placebo and other active antihistamines in patients who complained either from AR or chronic urticaria. METHODS: We systematically searched the Medline, Scopus, Web of Science, and Cochrane databases for randomized controlled trials (RCTs) evaluating bilastine effects on symptomatic hyper histaminic allergic conditions. We collected data on total symptoms scores (TSS), total nasal symptom scores (TNSS), discomfort associated with these allergic conditions measured by visual analog score (VAS), and quality of life (QOL) for AR and urticaria. Other outcomes such as clinical global impression and safety profiles were reported as well. We pooled the studies in a random effect model using RevMan 5.4 software. RESULTS: We included 9 RCTs comprising 3801 participants. The meta-analysis revealed that bilastine was superior to placebo, improving TSS, TNSS, VAS, and QOL in AR or chronic urticaria participants. Moreover, the bilastine was comparable to active antihistamines such as cetirizine, fexofenadine, and loratadine regarding mentioned outcomes. In addition, the novel drug was safe and tolerable with no difference in the incidence of adverse events with a placebo. CONCLUSIONS: Bilastine safely improved TSS in hyper histaminic allergic conditions involving nasal symptoms in AR. It decreases the discomfort associated with the disease resulting in improving the QOL of the participants.

Safety and Efficacy of Ruxolitinib in Patients with Myelofibrosis and Low Platelet Counts (50 - 100 × 109/L): Final Analysis of an Open-Label Phase 2 Study.

INTRODUCTION: Treatment options in patients with myelofibrosis (MF) presenting with thrombocytopenia are limited. Final results of the phase 2 study (NCT01348490) of ruxolitinib in patients with MF and low baseline platelet counts (50 - 100 × 109/L) are reported. PATIENTS AND METHODS: Patients received ruxolitinib 5 mg twice daily (BID), with optional up-titration to a maximum of 15 mg BID, provided platelet count remained ≥40 × 109/L. Assessments included spleen volume and length, Total Symptom Score (TSS), quality of life, and safety. RESULTS: Of 66 patients, 52 (78.8%) completed the first 24 weeks of treatment. Median (range) percentage change from baseline in spleen volume and TSS (coprimary endpoints) were -20.5% (-55.8% to 38.5%, n=51) and -39.8% (-98.6% to 226.4%, n=53), respectively; greatest median reductions were in the 10 mg BID final titrated dose group. Of patients achieving ≥35% or ≥10% reduction in spleen volume, 8/11 (72.7%) and 21/34 (61.8%), respectively, were in the 10 mg BID final titrated dose group. Thirty-seven of 65 patients (56.9%) had ≥20% improvement in TSS, and 35/66 patients (53.0%) were Patient Global Impression of Change responders. Treatment-emergent adverse events led to dose interruption in 17/66 patients (25.8%), most commonly thrombocytopenia (n=3). CONCLUSION: A starting dose of ruxolitinib 5 mg BID with gradual up-titration and dose optimization based on hematologic parameters and response was efficacious and generally well-tolerated in patients with MF and low platelet counts. Median improvement in spleen volume and symptoms was greatest for patients receiving ruxolitinib 10 mg BID.

Early intervention with Kan Jang® to treat upper-respiratory tract infections: A randomized, quadruple-blind study.

BACKGROUND AND AIM: Andrographis paniculata and Eleutherococcus senticosus preparations and their fixed combination, called Kan Jang®, are traditionally used for relieving symptoms of upper-respiratory tract infections (URTIs). This study aimed to assess the efficacy of early intervention with Kan Jang® on the relief and duration of inflammatory symptoms during the acute phase of the disease. EXPERIMENTAL PROCEDURE: A total of 179 patients with URTI symptoms received six Kan Jang® (daily dose of andrographolides: 60 mg) or placebo capsules a day for five consecutive days in this randomized, quadruple-blinded, placebo-controlled, two-parallel-group phase II study. The primary efficacy outcomes were the decrease in the acute-phase duration and the mean URTI symptoms score (sore throat, runny nose, nasal congestion, hoarseness, cough, headache, and fatigue). RESULTS: Early intervention with Kan Jang® significantly increased the recovery rate and reduced the number of sick leave days by >21% (0.64/day) relative to that observed in the placebo group (2.38 vs. 3.02 days, p = 0.0053). Kan Jang® significantly alleviated all URTI symptoms starting from the second day of treatment. A superior anti-inflammatory effect of Kan Jang® to that of placebo was also observed on the white blood cell count (p = 0.007) and erythrocyte sedimentation rate (p = 0.0258). Treatment with Kan Jang® was tolerated well. CONCLUSION: This study demonstrates that early intervention with Kan Jang® capsules reduces the recovery duration of patients by 21% and significantly relieves the severity of typical URTI symptoms.

Validation of a Modified Version of the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score.

BACKGROUND: Patients with myeloproliferative neoplasms (MPNs) suffer from chronic and progressive symptom burden. MPN trials capturing patient-reported symptoms routinely administer the MPN Symptom Assessment Form (SAF). The MPN-10 assesses 10 of the most clinically relevant symptoms, including fatigue and generates a Total Symptom Score (TSS). The original MPN-10 included a fatigue item from the Brief Fatigue Inventory (BFI). The myelofibrosis-specific symptom assessment tool called the MFSAF v4 utilizes a fatigue item developed to be consistent with other items within the SAF. This study sought to validate a modified version of the MPN-10 TSS using the SAF fatigue item for harmonization with MFSAF v4. METHODS: Survey data from two cohorts of patients with essential thrombocythemia, polycythemia vera, or myelofibrosis assessing MPN characteristics and symptom burden were used. RESULTS AND CONCLUSION: BFI and SAF fatigue items were highly correlated in raw score (Pearson r = 0.88), comparable in their severity categorizations (89% agreement for severe versus non-severe) and respective contributions to the TSS (both Cronbach's alpha = 0.89). Reliability of SAF fatigue was acceptable and independently associated with known disease-related characteristics (splenomegaly, low quality-of-life, and distress). Fatigue in patients with MPNs is measured with high similarity using the SAF fatigue item within the MPN-10 in harmonization with the MFSAF v4.

[The relationship between symptom burden and hematologic responses after treatment with interferon/hydroxyurea in patients with polycythemia vera].

Objective: To explore the relationship between symptom burden and hematologic responses after treatment with interferon and/or hydroxyurea in patients with polycythemia vera (PV) . Methods: Hematologic responses after continuous treatment with interferon and/or hydroxyurea for six months were evaluated in 190 patients with PV using the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-10 score) . In all patients, the PV diagnosis was based on the 2016 World Health Organization diagnostic definitions. Results: The study cohort comprised 93 (48.9% ) male and 97 (51.1% ) female patients. The median age at the time of MPN-10 assessment was 60 (32-82) years. The median MPN-10 score of the entire cohort was 9 (range, 0-67) . The median MPN-10 score of patients treated with interferon plus hydroxyurea (n=27) was 11 (0-67) , which was significantly higher than those of patients treated with interferon only (n=64) (6[0-56], P=0.019) or hydroxyurea only (n=99) (9[0-64], P=0.047) , whereas the median MPN-10 score was not significantly different between those treated with interferon only and hydroxyurea only (P=0.421) . The rate of severe symptom burden (i.e., any single symptom burden score ≥ 7 and/or total score ≥ 44) was 28.9% (55/190) in the entire cohort, whereas the rate of severe symptom burden was not significantly different among the interferon only (23.4% ) , hydroxyurea only (29.3% ) , and interferon plus hydroxyurea (40.7% ) groups (P>0.05 for all two-group comparisons) . When evaluating MPN-10 score, 37.4% (71/190) of the patients achieved complete hematologic remission (CHR) . Only 28.9% (55/190) patients had adequate disease control, defined as CHR without severe symptom burden. Reasons for inadequate disease control were evaluating blood counts alone, severe symptom burden alone, and evaluating blood counts accompanied with severe symptom burden in 42.1% (80/190) , 8.4% (16/190) , and 20.5% (39/190) of the patients, respectively. Compared to the patients with a platelet count ≤ 400×10(9)/L, those with a platelet count > 400×10(9)/L had a significantly higher rate of severe symptom burden (40.8% [20/49] vs 24.8% [35/141], P=0.044) and a higher median MPN-10 score (14[0-67] vs 7[0-56], P=0.038) . Platelet count > 400×10(9)/L was associated with an increased risk of severe symptom burden (hazard ratio, 2.089; 95% confidence interval, 1.052-4.147, P=0.035) . Conclusions: Symptoms related to disease after treatment with interferon and/or hydroxyurea were rather universal in patients with PV. Some patients still experienced severe symptom burden despite achieving CHR. Platelet count > 400×10(9)/L was associated with an increased risk of severe symptom burden in patients with PV treated with interferon and/or hydroxyurea.

First evaluation of a symbiotic food supplement in an allergen exposure chamber in birch pollen allergic patients.

BACKGROUND: Allergic rhinitis/rhinoconjunctivitis is the most common immune disease worldwide, but still largely underestimated, underdiagnosed, and undertreated. Dysbiosis and reduced microbial diversity is linked to the development of allergies, and the immunomodulatory effects of pro- and prebiotics might be used to counteract microbiome dysbiosis in allergy. Adequate symbiotic (multi-strain pro-, plus prebiotic) supplementation can be suggested as a complementary approach in the management of allergic rhinitis. OBJECTIVE: The effects of the daily intake of a symbiotic food supplement (combination of Lactobacillus acidophilus NCFM and Bifidobacterium lactis BL-04 with Fructo-Oligosaccharides) for 4 months in birch pollen allergic rhinoconjunctivitis patients were investigated for the first time in an allergen exposure chamber (AEC) allowing standardised, reproducible pollen exposure before and after intake. METHODS: Eligible patients were exposed to birch pollen (8000 pollen/m³ for 120 min) at the GA2LEN AEC, at baseline (V1) and final visit (V3) outside the season. The Total Symptom Score (TSS) and the scores for nose, eye, bronchial system, and others were evaluated every 10 min during exposure. Other secondary endpoints were the changes in well-being, Peak Nasal Inspiratory Flow (PNIF), lung function parameters, and safety. Co-primary endpoints were differences in Total Nasal Symptom Score (TNSS) and TSS after 120 min of exposure between both visits. Temporal evolution of symptom scores were analysed in an exploratory way using linear mixed effects models. RESULTS: 27 patients (mean age 45 years, 15% male) completed the study. Both co-primary endpoints showed significant improvement after intake of the symbiotic. Median TNSS and TSS were decreased 50% and 80% at 120 min (adjusted p-value = 0.025 and p < 0.01 respectively).All four symptom scores and the personal well-being, improved to a clinically relevant extent over time, visible by a weaker increase in symptoms during 120 min of the final birch pollen exposure. No relevant differences were observed for PNIF, PEF, and spirometry. There were no airway obstructions or lung restrictions before and after both exposures. Late phase reactions after exposure were reduced after V3, documenting a better birch pollen tolerability of the patients. The safety and tolerability profile of the symbiotic food supplement was excellent, no adverse events (AEs) were observed. CONCLUSIONS: This first evaluation of a symbiotic food supplement in an AEC in rhinoconjunctivitis patients with or without asthma induced by birch pollen revealed a significant beneficial effect, harnessing significant improvements of symptoms and well-being while maintaining an excellent safety and tolerability profile.

Loratadine vs Rupatadine: Unearthing the Capital Choice in Chronic Idiopathic Urticaria (CIU) - A Randomized Controlled Trial.

Background: Chronic Idiopathic Urticaria (CIU) is a debilitating disease characterised by almost daily presence of urticarial symptoms like short-lived wheals, itching, and erythema for at least 6 weeks without an identifiable cause there by leading to impairment of quality of life of the patient. Aim: To evaluate the efficacy and safety of loratadine and rupatadine in chronic idiopathic urticaria. Methods: This is a prospective, randomized, single-blind, parallel arm study conducted to evaluate the efficacy and safety of loratadine and rupatadine in patients with CIU. The study was registered prospectively with Clinical Trial registry of India (CTRI/2017/05/008624). Institutional Ethics Committee clearance was obtained. Written informed consent was obtained from all the participants before enrolment into the trial. The study was conducted in the outpatient department of Dermatology, SRM Medical College, Kattankulathur, Tamil Nadu, India, during the period from June 2017 to August 2018. Patients with CIU enrolled into the study based on inclusion-exclusion criteria were given the intervention drugs; Loratadine 10 mg once daily or rupatadine10 mg once daily orally for 6 weeks. Results: Rupatadine is more efficacious than loratadine in the reduction of Total Leucocyte Count, Differential Count and Absolute Eosinophil Count, the key determinants of allergy. Rupatadine also produced better improvement in Total symptom Score, Dermatology Life Quality Index in patients with CIU. Conclusion: Analysis of all the parameters of efficacy and safety establishes the probable superiority of rupatadine over loratadine for the treatment of urticaria.

Strong dose response after immunotherapy with PQ grass using conjunctival provocation testing.

BACKGROUND: Pollinex Quattro Grass (PQ Grass) is an effective, well-tolerated, short pre-seasonal subcutaneous immunotherapy to treat seasonal allergic rhinoconjunctivitis (SAR) due to grass pollen. In this Phase II study, 4 cumulative doses of PQ Grass and placebo were evaluated to determine its optimal cumulative dose. METHODS: Patients with grass pollen-induced SAR were randomised to either a cumulative dose of PQ Grass (5100, 14400, 27600 and 35600 SU) or placebo, administered as 6 weekly subcutaneous injections over 31-41 days (EudraCT number 2017-000333-31). Standardized conjunctival provocation tests (CPT) using grass pollen allergen extract were performed at screening, baseline and post-treatment to determine the total symptom score (TSS) assessed approximately 4 weeks after dosing. Three models were pre-defined (Emax, logistic, and linear in log-dose model) to evaluate a dose response relationship. RESULTS: In total, 95.5% of the 447 randomized patients received all 6 injections. A highly statistically significant (p < 0.0001), monotonic dose response was observed for all three pre-specified models. All treatment groups showed a statistically significant decrease from baseline in TSS compared to placebo, with the largest decrease observed after 27600 SU (p < 0.0001). The full course of 6 injections was completed by 95.5% of patients. Treatment-emergent adverse events were similar across PQ Grass groups, and mostly mild and transient in nature. CONCLUSIONS: PQ Grass demonstrated a strong curvilinear dose response in TSS following CPT without compromising its safety profile.

Transcriptome analysis and safety profile of the early-phase clinical response to an adjuvanted grass allergoid immunotherapy.

BACKGROUND: Specific immunotherapy is the only type of disease-modifying treatment, which induces rapid desensitization and long-term sustained unresponsiveness in patients with seasonal allergic rhinoconjunctivitis. The safety and tolerability of a new cumulative dose regimen of 35600 SU Grass MATA MPL for subcutaneous immunotherapy were assessed in pre-seasonal, single-blind, placebo controlled Phase I clinical study. Underlying immunological mechanisms were explored using transcriptome analysis of peripheral blood mononuclear cells. METHODS: Study subjects with a history of moderate to severe seasonal allergic rhinitis and/or conjunctivitis (SAR) due to grass (Pooideae) pollen exposure were randomized on a 1:1 ratio to receive either six 1.0 mL injections of cumulative dose regimen 35600 SU of Grass MATA MPL or placebo. The study consisted of three periods: screening, randomization and treatment and End of Study period. Blood samples were taken for clinical safety laboratory assessments and for the assessment of gene expression analysis during screening visit and End of Study visit. The safety statistics was calculated using Fisher's exact test. Delta Delta Ct method analysis of RT2 Profiler PCR Array gene expression results was used to calculate changes in gene expression level. Genes with the absolute value of log2 fold change greater than ±1.1 and p-value less than 0.05 were identified as differentially expressed and underwent IPA data analysis. RESULTS: The results of the study indicated that the higher cumulative dose regimen of the immunotherapy was well-tolerated. Changes in gene expression profile were associated with early immune responses implicating innate and adaptive immune mechanisms. Pathways and mechanistic network analysis via IPA mapped differentially expressed genes onto canonical pathways related to T cell differentiation, cytokine signalling and Th1/Th2 activation pathways. The transcriptome findings of the study could be further verified in large-scale field studies in order to explore their potential as predictive markers of successful immunotherapy. CONCLUSIONS: The higher dose cumulative regime 35600 SU of Grass MATA MPL vaccine was well tolerated and safe. Molecular markers IL-27, IL-10, IL-4, TNF, IFNγ, TGFß and TLR4 were the main predicted molecular drivers of the observed gene expression changes following early stages of SIT with Grass MATA MPL immunotherapy.

Symptom load assessment of Ph chromosome/BCR-ABL fusion gene negative myeloproliferative tumor patients at different efficacy evaluation periods / 国际肿瘤学杂志

Objective@#To observe the disease type and the changes of symptom load during treatment of patients with Ph chromosome/BCR-ABL fusion gene negative myeloproliferative neoplasm (MPN).@*Methods@#A total of 84 patients with MPN diagnosed from May 2017 to January 2019 in People′s Hospital of Longhua District of Shenzhen were selected, and were divided into polycythemia vera (PV) group, essential thrombocyhemia (ET) group, and myelofibrosis (PMF) group according to their subtypes, with 28 cases in each group. The scores of MPN-SAF-TSS were compared among the three groups. Besides, the scores of the scale (myeloproliferative neoplasm symptom assessment form total symptom score, MPN-SAF-TSS) in different treatment periods (at the time of the visit, when the disease progressed, when the disease was stable, when the clinical improvement was made, when the partial remission was completed, at the time of remission and recurrence) were also compared.@*Results@#At the time of initial diagnosis, there were significant differences in the incidences of symptom burdens among the three groups of MPN patients with abdominal fullness (χ2=6.095, P=0.047), abdominal discomfort (χ2=7.342, P=0.025), poor mobility (χ2=13.029, P=0.001), inattention (χ2=6.099, P=0.047), pruritus (χ2=6.956, P=0.031), bone pain (χ2=7.807, P=0.020), fever (χ2=8.000, P=0.018) and weight loss (χ2=27.340, P<0.001). The incidences of poor mobility (85.71%, 24/28), inattention (67.86%, 19/28) and weight loss (82.14%, 23/28) in PMF group were significantly higher than those in PV group [42.86% (12/28), 39.29% (11/28), 35.71% (10/28)] and ET group [46.43% (13/28), 39.29% (11/28), 14.29% (4/28)] (all P<0.05). The incidences of abdominal discomfort (75.00%, 21/28) and bone pain (60.71%, 17/28) in PMF group were higher than those in PV group [39.29% (11/28), 25.00% (7/28)] (both P<0.05). The incidences of abdominal fullness (89.29%, 25/28) and fever (42.86%, 12/28) in PMF group were higher than those in ET group [60.71% (17/28), 10.71% (3/28)] (both P<0.05). The incidence of pruritus in PV group (71.43%, 20/28) was higher than that in ET group (42.86%, 12/28) and PMF group (39.29%, 11/28) (both P<0.05). Symptom load scores of patients with fatigue (χ2=368.594, P<0.001), abdominal fullness (χ2=261.312, P<0.001), abdominal discomfort (χ2=195.629, P<0.001), poor mobility (χ2=217.862, P<0.001), lack of concentration (χ2=280.664, P<0.001), night sweats (χ2=239.650, P<0.001), pruritus (χ2=254.418, P<0.001), bone pain (χ2=180.291, P<0.001), fever (χ2=231.613, P<0.001) and weight loss (χ2=227.831, P<0.001) were significantly different during different therapeutic periods. The fatigue symptom load score was higher when the disease progressed than that at the time of the visit (P<0.05), and the symptom score of abdominal fullness was lower than that at the time of visit (P<0.05). Symptom load scores of weakness and pruritus when the condition was stable was lower than those when the disease progressed (both P<0.05). When the clinical improvement was made, symptom load scores of weakness, abdominal discomfort, inattention, night sweats, weight loss were lower than those when the disease was stable (all P<0.05). Symptom load scores of abdominal fullness, poor mobility, inattention, night sweats and pruritus in partial remission period decreased compared to temporary improvement period (all P<0.05). Compared to the partial remission period, the symptom load scores of weakness, abdominal fullness, night sweats, pruritus, bone pain and weight loss in complete remission period were lower (all P<0.05). At last, symptom load scores of weakness, abdominal fullness, abdominal discomfort, poor mobility, inattention, night sweats, pruritus, bone pain, fever and weight loss in recurrence period were higher than those in complete remission period (all P<0.05).@*Conclusion@#There are several differences in the main clinical symptoms among patients with different MPN subtypes, and there are significant changes in the main clinical symptoms as the disease progresses or turns around.

Symptom load assessment of Ph chromosome/ BCR-ABL fusion gene negative myeloproliferative tumor patients at different efficacy evaluation periods / 国际肿瘤学杂志

Objective To observe the disease type and the changes of symptom load during treatment of patients with Ph chromosome/ BCR-ABL fusion gene negative myeloproliferative neoplasm (MPN). Methods A total of 84 patients with MPN diagnosed from May 2017 to January 2019 in People's Hospital of Longhua Dis-trict of Shenzhen were selected,and were divided into polycythemia vera (PV)group,essential thrombocy-hemia (ET)group,and myelofibrosis (PMF)group according to their subtypes,with 28 cases in each group. The scores of MPN-SAF-TSS were compared among the three groups. Besides,the scores of the scale (myelo-proliferative neoplasm symptom assessment form total symptom score,MPN-SAF-TSS)in different treatment periods (at the time of the visit,when the disease progressed,when the disease was stable,when the clinical improvement was made,when the partial remission was completed,at the time of remission and recurrence) were also compared. Results At the time of initial diagnosis,there were significant differences in the inci-dences of symptom burdens among the three groups of MPN patients with abdominal fullness (χ2 = 6. 095,P =0. 047),abdominal discomfort (χ2 = 7. 342,P = 0. 025),poor mobility (χ2 = 13. 029,P = 0. 001),inatten-tion (χ2 = 6. 099,P = 0. 047),pruritus (χ2 = 6. 956,P = 0. 031),bone pain (χ2 = 7. 807,P = 0. 020),fever (χ2 = 8. 000,P = 0. 018)and weight loss (χ2 = 27. 340,P < 0. 001). The incidences of poor mobility (85. 71％,24 / 28),inattention (67. 86％,19 / 28)and weight loss (82. 14％,23 / 28)in PMF group were significantly higher than those in PV group [42. 86％ (12 / 28),39. 29％ (11 / 28),35. 71％ (10 / 28)]and ET group [46. 43％ (13 / 28),39. 29％ (11 / 28),14. 29％ (4 / 28)](all P < 0. 05). The incidences of abdominal discomfort (75. 00％,21 / 28)and bone pain (60. 71％,17 / 28)in PMF group were higher than those in PV group [39. 29％ (11 / 28),25. 00％ (7 / 28)](both P < 0. 05). The incidences of abdominal fullness (89. 29％,25 / 28)and fever (42. 86％,12 / 28)in PMF group were higher than those in ET group [60. 71％ (17 / 28),10. 71％ (3 / 28)](both P < 0. 05). The incidence of pruritus in PV group (71. 43％, 20 / 28)was higher than that in ET group (42. 86％,12 / 28)and PMF group (39. 29％,11 / 28)(both P <0. 05). Symptom load scores of patients with fatigue (χ2 = 368. 594,P < 0. 001),abdominal fullness (χ2 =261. 312,P < 0. 001),abdominal discomfort (χ2 = 195. 629,P < 0. 001),poor mobility (χ2 = 217. 862,P <0. 001),lack of concentration (χ2 = 280. 664,P < 0. 001),night sweats (χ2 = 239. 650,P < 0. 001),pruri-tus (χ2 = 254. 418,P < 0. 001),bone pain (χ2 = 180. 291,P < 0. 001),fever (χ2 = 231. 613,P < 0. 001) and weight loss (χ2 = 227. 831,P < 0. 001)were significantly different during different therapeutic periods. The fatigue symptom load score was higher when the disease progressed than that at the time of the visit (P <0. 05),and the symptom score of abdominal fullness was lower than that at the time of visit (P < 0. 05). Symp-tom load scores of weakness and pruritus when the condition was stable was lower than those when the disease progressed (both P < 0. 05). When the clinical improvement was made,symptom load scores of weakness, abdominal discomfort,inattention,night sweats,weight loss were lower than those when the disease was stable (all P < 0. 05). Symptom load scores of abdominal fullness,poor mobility,inattention,night sweats and pruri-tus in partial remission period decreased compared to temporary improvement period (all P < 0. 05). Compared to the partial remission period,the symptom load scores of weakness,abdominal fullness,night sweats,pruri-tus,bone pain and weight loss in complete remission period were lower (all P < 0. 05). At last,symptom load scores of weakness,abdominal fullness,abdominal discomfort,poor mobility,inattention,night sweats,pruri-tus,bone pain,fever and weight loss in recurrence period were higher than those in complete remission period (all P < 0. 05). Conclusion There are several differences in the main clinical symptoms among patients with different MPN subtypes,and there are significant changes in the main clinical symptoms as the disease progresses or turns around.

Predictivity of clinical efficacy of sublingual immunotherapy (SLIT) based on sensitisation pattern to molecular allergens in children with allergic rhinoconjunctivitis.

BACKGROUND: The diagnostic and therapeutic approach to grass pollen allergy is now possible by detecting specific IgE (sIgE) to its allergenic components. AIM: To evaluate the correlation between the sensitisation to different molecular Phleum pratense (Phl p) allergens and clinical efficacy of SLIT. METHODS: The pilot study included 36 patients affected by allergic rhinoconjunctivitis, all treated with SLIT actively. We performed serum analysis of sIgE to Phl p 1, 2, 4, 5, 6, 7, 11 and 12. The Average Rhinoconjunctivitis Total Symptom Score (ARTSS) and the Average Combined Score (ACS) were evaluated before and after one year of immunotherapy. RESULTS: Three different groups of sensitisation were defined based on the range of IgE reactivity to Phleum pratense allergens at baseline: group I (sIgE reactive to 1-3 allergens); group II (sIgE reactive to 4-5 allergens); and group III (sIgE reactive to 6-8 allergens). At T0 ACS was 1.79±0.18 in group I; 1.81±0.23 in group II; and 1.95±0.34 in group III. At T1 ACS was 0.85±0.55 in group I; 1.01±0.31 in group II; and 1.44±0.39 in group III. At T1 there was a significant improvement of ARTSS and ACS for group I (p=0.001). CONCLUSIONS: Sublingual immunotherapy with a grass pollen is efficacious irrespective of the patients' baseline sensitisation to either single or multiple grass pollen molecular allergens. We found that patients with few sensitisations have a greater improvement in combined symptom and medication score. SLIT improves the clinical course of allergic patients although new sensitisations may appear.

Efficacy and safety of bilastine in Japanese patients with chronic spontaneous urticaria: A multicenter, randomized, double-blind, placebo-controlled, parallel-group phase II/III study.

BACKGROUND: Bilastine, a novel non-sedating second-generation H1-antihistamine, has been widely used in the treatment of allergic rhinoconjunctivitis and urticaria with a recommended dose of 20 mg once daily in most European countries since 2010. We evaluated its efficacy and safety in Japanese patients with chronic spontaneous urticaria (CSU). METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled phase II/III study (trial registration No. JapicCTI-142574). Patients (age, 18-74 years) were randomly assigned to receive bilastine 20 mg, 10 mg or placebo once daily for 2 weeks. The primary efficacy endpoint was the change from baseline (Day -3 to 0) in total symptom score (TSS) at 2 weeks (Day 8-14), consisting of the itch and rash scores. RESULTS: A total of 304 patients were randomly allocated to bilastine 20 mg (101 patients), bilastine 10 mg (100 patients), and placebo (103 patients). The changes in TSS at 2 weeks were significantly decreased by bilastine 20 mg than did placebo (p < 0.001), demonstrating the superiority of bilastine 20 mg. Bilastine 10 mg also showed a significant difference from placebo (p < 0.001). The TSS changes for the bilastine showed significant improvement from Day 1, and were maintained during the treatment period. The Dermatology Life Quality Index scores were also improved in bilastine than in placebo. The bilastine treatments were safe and well tolerated. CONCLUSIONS: Two-week treatment with bilastine (20 or 10 mg) once daily was effective and tolerable in Japanese patients with CSU, demonstrating an early onset of action.

Day-to-day variability of post-concussion-like symptoms reported over time by a non-concussed cohort.

PRIMARY OBJECTIVE: To explore the change (trend) in post-concussion-like symptoms reported over time. RESEARCH DESIGN: Longitudinal study. METHODS AND PROCEDURES: University students aged 18-30 years self-reported their symptoms experienced on a daily basis. Each participant was contacted via a text message each day during one of three pre-defined time zones to complete the Sport Concussion Assessment Tool 2 (SCAT2) post-concussion symptom scale on 7 consecutive days. MAIN OUTCOMES AND RESULTS: One hundred and ten (26 males and 84 females) students completed the study on all 7 days. Only two meaningful clusters emerged and comprised of a total of 105 participants. The primary cluster included 85 participants who showed a relatively stable pattern in their symptoms reported over time. Meanwhile, a second cluster comprised of 20 participants who demonstrated a decreasing trend in the reported symptom scores. CONCLUSIONS: The data indicated that non-concussed participants exhibited considerable individual variability in the symptom scores reported over time. However, some participants showed a systematic decreasing trend in their symptom scores reported over the 7 days. Caution must be exercised in interpreting the serial symptom scores that are obtained following a concussion, given that this study was conducted in a non-concussed cohort.

The Influence of Psychological and Lifestyle Factors on the Reporting of Postconcussion-Like Symptoms.

Self-reported symptoms are an integral part of the assessment and management of a sports-related concussion. However, postconcussion-like symptoms are reported by non-concussed individuals. Moreover, the current best practice in the reporting of symptoms does not take into account the potential influence of psychological and lifestyle factors. This study aimed to explore the influence of these factors on the reporting of postconcussion-like symptoms. University students (N= 603) completed the Sport Concussion Assessment Tool 2 postconcussion symptom scale along with other predictor variables via a cross-sectional web-based survey. Linear regression analyses revealed six modifiers contributing to the total symptom score with the strongest being alcohol consumption (Estimate = 2.75, p < .001). Following these findings, clinicians need to exercise caution when interpreting the symptom scores for making decisions on the return-to-play (RTP). A failure to do so may lead the health professional to either prematurely RTP or not clear the concussed athlete to resume their sport.

Efficacy of a short course of specific immunotherapy in patients with allergic rhinoconjunctivitis to ragweed pollen.

BACKGROUND: Specific immunotherapy acts to modify the underlying cause of allergic rhinoconjunctivitis. Addition of adjuvants, such as monophosphoryl lipid A (MPL), might allow for efficacious and safe treatment with only 4 injections administered preseasonally, which is in contrast to most available schedules requiring long injection courses. OBJECTIVE: The primary objective was to assess the clinical efficacy of Ragweed MATA MPL (short ragweed pollen allergoid adsorbed to L-Tyrosine + MPL) versus placebo in reducing allergic rhinoconjunctivitis symptoms caused by ragweed pollen in an environmental exposure chamber (EEC) 3 weeks after treatment. METHODS: This was a randomized, double-blind, placebo-controlled phase IIb study to evaluate the clinical efficacy and safety of Ragweed MATA MPL compared with placebo by using controlled ragweed pollen exposure in an EEC. Two hundred twenty-eight patients with a history of ragweed allergy and positive skin prick test responses to ragweed were randomized and received 4 weekly injections of active treatment or placebo. Total nasal and nonnasal symptom scores were obtained in the EEC before and after treatment. RESULTS: Mean improvement in total symptom scores in the Ragweed MATA MPL group was statistically significantly greater than in the placebo group (relative mean improvement of active vs placebo, 48%; P < .05; median improvement, 82%). The majority of adverse events (AEs) experienced by subjects were mild injection-site reactions. No severe systemic AEs or serious AEs occurred during the study. CONCLUSION: This study demonstrated that an ultrashort course of Ragweed MATA MPL is efficacious in reducing allergy symptoms in patients with seasonal allergic rhinitis and that it is well tolerated.